Benefits of flavonoid and metronidazole use after excisional hemorrhoidectomy: a randomized double-blind clinical trial.

BACKGROUND: Excisional hemorrhoidectomy remains the most effective treatment for a significant group of patients with hemorrhoids, despite the potential for postoperative pain. The purpose of this study was to evaluate the effects of flavonoid and metronidazole use in the postoperative period on patients undergoing excisional hemorrhoidectomy. METHODS: A double-blind randomized clinical study was performed. Sixty-eight patients underwent excisional hemorrhoidectomy and were randomized into 4 groups of 17 patients each to receive double-placebo (G1), metronidazole plus placebo (G2), flavonoids plus placebo (G3) or metronidazole plus flavonoids (G4) in the postoperative period. A standard analgesic protocol was offered equally for all groups. Postoperative pain, bleeding, edema, pruritus and tenesmus were evaluated during the following three periods: from immediately after the operation until postoperative day (POD)7, from POD 8 to POD 14, and from POD 15 to POD 30. The patients were required to complete symptom questionnaires and to attend postoperative follow-up on PODs 7, 14 and 30. The effect of each drug was assessed for each symptom, and the groups were compared with each other and over time. RESULTS: There was less severe pain in all postoperative periods in the groups using flavonoids (G3 and G4, both p < 0.0001), with an observed synergistic effect of flavonoids combined with metronidazole during the first 14 days after surgery (p < 0.0001). Flavonoid use was also associated with decreased bleeding (G3, p = 0.031 and G4, p = 0.016) between the first and second postoperative weeks CONCLUSIONS: The use of flavonoids alone and in combination with metronidazole resulted in a reduction of most symptoms, particularly pain, after excisional hemorrhoidectomy. TRIAL REGISTRATION: The present study was registered in the SISNEP (document CAAE-0035.0.240.000-11), after approval by the research ethics committee (CEP) of the Hospital Felício Rocho (protocol nº393 / 11).

Phase Transitions in Phospholipid Monolayers: Theory Versus Experiments.

The Doniach lattice gas (DLG) represents a ternary-mixture statistical model, whose components, water molecules (w), ordered-chain lipids (o), and disordered-chain lipids (d)-the latter carrying a high degenerescence ω ≫ 1-are located at each site of a two-dimensional lattice. The DLG model was introduced to describe phospholipid Langmuir films at the air-water interface and can be mapped into a spin-1 model, with the single-site states s i = 0, +1, and -1 representing the three types of molecules in the system (w, o, and d), respectively. The model allows lipid-density fluctuations and has been analyzed at the mean-field approximation (Guidi, H. S.; Henriques, V. B. Phys. Rev. E 2014, 90, 052705) as well as at the pair approximation (de Oliveira, F. O.; Tamashiro, M. N. Phys. Rev. E 2019, 99, 012147). In this work, we focus on performing an explicit comparison of the theoretical predictions obtained for the DLG model at the pair approximation with isothermal monolayer compression experiments (Nielsen, L. K.; Bjørnholm, T.; Mouritsen, O. G. Langmuir 2007, 23, 11684) for the two most commonly studied saturated zwitterionic phospholipids, DMPC (1,2-dimyristoyl- sn-glycero-3-phosphocholine) and DPPC (1,2-dipalmitoyl- sn-glycero-3-phosphocholine). The model parameters obtained by fitting to the experimental data yield phase diagrams that are qualitatively consistent with the observed phase transitions on DMPC and DPPC monolayers, with the absence of a low-density gas phase. Quantitative agreement, however, was less significant partially because of the challenging reproducibility of Langmuir monolayer compression experiments, claimed in the literature to be influenced by kinetic effects.

Vistusertib (dual m-TORC1/2 inhibitor) in combination with paclitaxel in patients with high-grade serous ovarian and squamous non-small-cell lung cancer.

Background: We have previously shown that raised p-S6K levels correlate with resistance to chemotherapy in ovarian cancer. We hypothesised that inhibiting p-S6K signalling with the dual m-TORC1/2 inhibitor in patients receiving weekly paclitaxel could improve outcomes in such patients. Patients and methods: In dose escalation, weekly paclitaxel (80 mg/m2) was given 6/7 weeks in combination with two intermittent schedules of vistusertib (dosing starting on the day of paclitaxel): schedule A, vistusertib dosed bd for 3 consecutive days per week (3/7 days) and schedule B, vistusertib dosed bd for 2 consecutive days per week (2/7 days). After establishing a recommended phase II dose (RP2D), expansion cohorts in high-grade serous ovarian cancer (HGSOC) and squamous non-small-cell lung cancer (sqNSCLC) were explored in 25 and 40 patients, respectively. Results: The dose-escalation arms comprised 22 patients with advanced solid tumours. The dose-limiting toxicities were fatigue and mucositis in schedule A and rash in schedule B. On the basis of toxicity and pharmacokinetic (PK) and pharmacodynamic (PD) evaluations, the RP2D was established as 80 mg/m2 paclitaxel with 50 mg vistusertib bd 3/7 days for 6/7 weeks. In the HGSOC expansion, RECIST and GCIG CA125 response rates were 13/25 (52%) and 16/25 (64%), respectively, with median progression-free survival (mPFS) of 5.8 months (95% CI: 3.28-18.54). The RP2D was not well tolerated in the SqNSCLC expansion, but toxicities were manageable after the daily vistusertib dose was reduced to 25 mg bd for the following 23 patients. The RECIST response rate in this group was 8/23 (35%), and the mPFS was 5.8 months (95% CI: 2.76-21.25). Discussion: In this phase I trial, we report a highly active and well-tolerated combination of vistusertib, administered as an intermittent schedule with weekly paclitaxel, in patients with HGSOC and SqNSCLC. Clinical trial registration: ClinicialTrials.gov identifier: CNCT02193633.

First record of soybean stem fly Melanagromyza sojae (Diptera: Agromyzidae) in Paraguay confirmed by molecular evidence.

We provided the first scientific record of Melanagromyza sojae (Zehntner, 1900), through molecular characterization of partial mtDNA COI gene, that confirms the occurrence of this pest in Paraguay. Previously reported in Brazil, an outbreak of larvae of M. sojae known as the soybean stem fly (SSF) that belongs to the family Agromyzidae, was also noted in soybean fields from the Canindeyú, Alto Paraná and Itapúa Departments in Paraguay. This pest is highly polyphagous, attacking various host plant species from the family Fabaceae, such as soybean and other beans. The implications of SSF detection in Paraguay are discussed in relation to the current soybean cultivation practices from this agriculturally important South American region, including Brazil.

The effect of an inhibitor of gut serotonin (LP533401) during the induction of periodontal disease.

BACKGROUND AND OBJECTIVE: LP533401 is an inhibitor of tryptophan hydroxylase 1, which regulates serotonin production in the gut. Previous work indicates that LP533401 has an anabolic effect in bone. Thus, we hypothesized that inhibition of gut serotonin production may modulate the host response in periodontal disease. In this study, we aimed to analyze the effects of LP533401 in a rat periodontitis model to evaluate the role of gut serotonin in periodontitis pathophysiology. MATERIAL AND METHODS: Twenty-four rats were divided into three groups: treated group (T: ligature-induced periodontal disease and LP533401, 25 mg/kg/d) by gavage; ligature group (L: ligature-induced periodontal disease only); and control group (C: without ligature-induced periodontal disease). After 28 d, radiographic alveolar bone support was measured on digital radiographs, and alveolar bone volume fraction, tissue mineral density and trabeculae characteristics were quantified by microcomputed tomography in the right hemi-mandible. Left hemi-mandibles were decalcified and alveolar bone loss, attachment loss and area of collagen in the gingiva were histologically analyzed. RESULTS: Significant difference between the L and C groups was found, confirming that periodontal disease was induced. We observed no difference between the T and L groups regarding alveolar bone destruction and area of collagen. CONCLUSION: LP533401 (25 mg/kg/d) for 28 d does not prevent bone loss and does not modulate host response in a rat model of induced periodontal disease.

Correlation and path analysis of biomass sorghum production.

Sorghum biomass is an interesting raw material for bioenergy production due to its versatility, potential of being a renewable energy source, and low-cost of production. The objective of this study was to evaluate the genetic variability of biomass sorghum genotypes and to estimate genotypic, phenotypic, and environmental correlations, and direct and indirect effects of seven agronomic traits through path analysis. Thirty-four biomass sorghum genotypes and two forage sorghum genotypes were cultivated in a randomized block design with three replicates. The following morpho-agronomic traits were evaluated: flowering date, stem diameter, number of stems, plant height, number of leaves, green mass production, and dry matter production. There were significant differences at the 1% level for all traits. The highest genotypic correlation was found between the traits green mass production and dry matter production. The path analysis demonstrated that green mass production and number of leaves can assist in the selection of dry matter production.

Nanotopography drives stem cell fate toward osteoblast differentiation through α1ß1 integrin signaling pathway.

The aim of our study was to investigate the osteoinductive potential of a titanium (Ti) surface with nanotopography, using mesenchymal stem cells (MSCs) and the mechanism involved in this phenomenon. Polished Ti discs were chemically treated with H2 SO4 /H2 O2 to yield nanotopography and rat MSCs were cultured under osteogenic and non-osteogenic conditions on both nanotopography and untreated polished (control) Ti surfaces. The nanotopography increased cell proliferation and alkaline phosphatase (Alp) activity and upregulated the gene expression of key bone markers of cells grown under both osteogenic and non-osteogenic conditions. Additionally, the gene expression of α1 and ß1 integrins was higher in cells grown on Ti with nanotopography under non-osteogeneic condition compared with control Ti surface. The higher gene expression of bone markers and Alp activity induced by Ti with nanotopography was reduced by obtustatin, an α1ß1 integrin inhibitor. These results indicate that α1ß1 integrin signaling pathway determines the osteoinductive effect of nanotopography on MSCs. This finding highlights a novel mechanism involved in nanosurface-mediated MSCs fate and may contribute to the development of new surface modifications aiming to accelerate and/or enhance the process of osseointegration.

Spectroscopy of 26F to probe proton-neutron forces close to the drip line.

A long-lived J(π) = 4(1)(+) isomer, T(1/2) = 2.2(1) ms, has been discovered at 643.4(1) keV in the weakly bound (9)(26)F nucleus. It was populated at Grand Accélérateur National d'Ions Lourds in the fragmentation of a (36)S beam. It decays by an internal transition to the J(π) = 1(1)(+) ground state [82(14)%], by ß decay to (26)Ne, or ß-delayed neutron emission to (25)Ne. From the ß-decay studies of the J(π) =1(1)(+) and J(π) = 4(1)(+) states, new excited states have been discovered in (25,26)Ne. Gathering the measured binding energies of the J(π) = 1(1)(+) -4(1)(+) multiplet in (9)(26)F, we find that the proton-neutron π0d(5/2)ν0d(3/2) effective force used in shell-model calculations should be reduced to properly account for the weak binding of (9)(26)F. Microscopic coupled cluster theory calculations using interactions derived from chiral effective field theory are in very good agreement with the energy of the low-lying 1(1)(+), 2(1)(+), 4(1)(+) states in (26)F. Including three-body forces and coupling to the continuum effects improve the agreement between experiment and theory as compared to the use of two-body forces only.

Phenotypic integration in flowers of neotropical lianas: diversification of form with stasis of underlying patterns.

Phenotypic integration is essential to the understanding of organismal evolution as a whole. In this study, a phylogenetic framework is used to assess phenotypic integration among the floral parts of a group of Neotropical lianas. Flowers consist of plant reproductive organs (carpels and stamens), usually surrounded by attractive whorls (petals and sepals). Thus, flower parts might be involved in different functions and developmental constraints, leading to conflicting selective forces. We found that Bignonieae flowers have very similar patterns of variance/covariance among traits and that such patterns are uncorrelated with the phylogenetic relationships between species. However, in spite of pattern stasis, our results also indicate that diversification of floral morphology in this group has occurred throughout the evolution of magnitudes of correlation among traits. Thus, we suggest that stabilizing selection has played an important role in phenotypic integration, resulting in the long-term stasis of covariance patterns underlying flower diversification during the ca. 50 Myr of evolution of Bignonieae. This is the first report of long-term stasis in the phenotypic integration of angiosperms, suggesting that patterns of floral morphology can be recognizable as specific attributes of distinct botanical families.

A new species of Atrichopleura Bezzi (Diptera, Empididae, Empidinae) from Ceará, Brazil.

Atrichopleura Bezzi, 1909 occurs in different regions of the Southern Hemisphere (24 Neotropical species, 2 Afrotropical species and 2 Australasian species). A new species collected in the Brazilian state of Ceará, A. acuminata sp. nov. is described and illustrated. This is the first record of the genus from northeastern Brazil. A modified key to the five Brazilian species is presented.

Insect (Hexapoda) Diversity in the Oceanic Archipelago of Fernando de Noronha, Brazil: Clusiidae (Diptera).

For the first time, Clusiidae (Diptera) species are recorded from the oceanic Archipelago Fernando de Noronha, Brazil. They are represented by three genera and seven species: Czernyola fumialula sp. nov., Heteromeringia czernyi Kertsz, 1903, Sobarocephala araujoi sp. nov., S. finnilaei Frey, 1918, S. icmbio sp. nov., S. protea Lonsdale & Marshall, 2012, and S. sp. For S. icmbio sp. nov., the aggregation behavior at night was observed on the undersides of broad leaves, females contained an average of 71 eggs, and flight interception traps correlated a positive linear relationship with precipitation seasonally. An illustrated key is presented for all species of the Archipelago.

Evidence of the participation of electronic excited states in the mechanism of positronium formation in substitutional Tb(1-x)Eu(x)(dpm)3 solid solutions studied by optical and positron annihilation spectroscopies.

Positronium formation in the bimary molecular solid solutions Tb(1-x)Eu(x) (dpm)(3) (dpm = dipivaloylmethanate) has been investigated. A strong linear correlation between the (5)D(4) Tb(iii) energy level excited state lifetime and the positronium formation probability has been observed. This correlation indicates that the ligand-to-metal charge transfer LMCT states act in both luminescence quenching and positronium formation inhibition, as previously proposed. A kinetic mechanism is proposed to explain this correlation and shows that excited electronic states have a very important role in the positronium formation mechanism.

[Considerations on photoprotection and skin disorders]. / Photoprotection et maladies cutanées.

Excessive exposure to solar or artificial sources of UV radiation is deleterious to the skin and can cause or worsen several diseases. Detrimental effects of UV radiation exert an important role in the development of skin cancers, cause alterations on the immune response, and act as a trigger or aggravating factor for pigmentary disorders. A group of measures, including education, change of habits, use of physical barriers and sunscreens constitutes a significant part of the treatment of many skin disorders and are valuable preventive tools. This article summarizes the relevant studies addressing these issues, emphasizing the many aspects of photoprotection.

Transcultural adaptation of the filial responsibility interview schedule for Brazil.

BACKGROUND: In developed countries, filial responsibility in relation to caring for elderly parents has been systematically studied. In Brazil and other developing countries, however, it is a relatively new topic and has not yet been included in the research agenda on ageing. OBJECTIVE: To describe the process of cross-cultural adaptation of the qualitative phase of the filial responsibility interview schedule into Brazilian Portuguese. METHODS: An expert committee of six team members participated in the study. In addition, individual interviews were held with 11 caregivers of older persons to evaluate the quality of the final Portuguese version of the schedule. The process included examining conceptual, item, semantic and operational equivalencies. Conceptual and item equivalencies were based on a literature review and on discussions with the expert committee. Semantic equivalence was attained through translation, back-translation, expert committee evaluation and pre-testing. The final version was pre-tested in caregivers of older persons enrolled in the home care programme of a primary health care service in Southern Brazil. RESULTS: Conceptual, item, semantic and operational equivalencies were attained. Through the interviews, responses to the open-ended questions concerning filial responsibility in the care for elderly parents pertained to the following categories: possibility of institutionalization of elderly parents, caregiver expectations, difficulties in being a child caregiver and responsibility as a natural process. CONCLUSION: The Portuguese version presented good semantic equivalence and the results showed that the concepts and items are applicable to the Brazilian context.

Prolate-spherical shape coexistence at N=28 in 44S.

The structure of 44S has been studied by using delayed γ and electron spectroscopy. The decay rates of the 02+ isomeric state to the 2(1)+ and 0(1)+ states, measured for the first time, lead to a reduced transition probability B(E2: 2(1)+→0(2)+)=8.4(26) e(2) fm4 and a monopole strength ρ2(E0: 0(2)+→0(1)+)=8.7(7)×10(-3). Comparisons to shell model calculations point towards prolate-spherical shape coexistence, and a two-level mixing model is used to extract a weak mixing between the two configurations.

CD73 as a target to improve temozolomide chemotherapy effect in glioblastoma preclinical model.

Glioblastoma is the most devastating primary brain tumor and effective therapies are not available. Treatment is based on surgery followed by radio and chemotherapy with temozolomide (TMZ), but TMZ increases patient survival only by 2 months. CD73, an enzyme responsible for adenosine production, emerges as a target for glioblastoma treatment. Indeed, adenosine causes tumor-promoting actions and CD73 inhibition increases sensitivity to TMZ in vitro. Here, a cationic nanoemulsion to nasal delivery of siRNA CD73 (NE-siRNA CD73) aiming glioblastoma treatment was employed alone or in combination with TMZ. In vitro, two glioblastoma cell lines (C6 and U138MG) with a chemo-resistant profile were used. Treatment alone with NE-siRNA CD73 reduced C6 and U138MG glioma cell viability by 70% and 25%, respectively. On the other hand, when NE-siRNA + TMZ combined treatment was employed, a reduction of 85% and 33% of cell viability was observed. Notably, treatment with NE-siRNA CD73 of glioma-bearing Wistar rats reduced tumor size by 80%, 60% more than the standard chemotherapy with TMZ, but no synergistic or additive effect was observed in vivo. Additionally, NE-siRNA CD73, TMZ or combined therapy decreased adenosine levels in liquor confirming the importance of this nucleoside on in vivo GB growth. Finally, no hemolytic potential was observed. These results suggest that nasal administration of NE-siRNA CD73 exhibits higher antiglioma effect when compared to TMZ. However, no synergistic or additive in vivo was promoted by the therapeutic regimen employed in this study.

Nasal Administration of Cationic Nanoemulsions as CD73-siRNA Delivery System for Glioblastoma Treatment: a New Therapeutical Approach.

Glioblastoma is the most devastating primary brain tumor. Effective therapies are not available, mainly due to high tumor heterogeneity, chemoresistance, and the difficulties imposed by blood-brain barrier. CD73, an enzyme responsible for adenosine (ADO) production, is overexpressed in cancer cells and emerges as a target for glioblastoma treatment. Indeed, ADO causes a variety of tumor-promoting actions, particularly by inducing tumor immune escape, whereas CD73 inhibition impairs tumor progression. Here, a cationic nanoemulsion to deliver CD73siRNA (NE-siRNA CD73R) via nasal route aiming glioblastoma treatment was developed. NE-siRNA CD73R was uptaken by glioma cells in culture, resulting in a parallel 60-80% decrease in AMPase activity and 30-50% in cell viability. Upon nasal delivery, NE-siRNA CD73R was detected in rat brain and serum. Notably, treatment with CD73siRNA complexes of glioma-bearing Wistar rats reduced tumor growth by 60%. Additionally, NE-siRNA CD73R treatment decreased 95% ADO levels in liquor and tumor CD73 expression, confirming in vivo CD73 silencing. Finally, no toxicity was observed in either primary astrocytes or rats with this cationic nanoemulsion. These results suggest that nasal administration of cationic NE as CD73 siRNA delivery system represents a novel potential treatment for glioblastoma. Graphical Abstract Glioblastoma is the most common and devastating form of primary brain tumor. CD73, a protein involved in cell-cell adhesion and migration processes and also responsible for extracellular adenosine (ADO) production, is overexpressed by glioma cells and emerges as an important target for glioma treatment. Indeed, ADO participates in tumor immune escape, cell proliferation, and angiogenesis, and CD73 inhibition impairs those processes. Here, a cationic nanoemulsion to deliver CD73 siRNA (NE-siRNA CD73R) via nasal route aiming glioblastoma treatment was developed. NE-siRNA CD73R knockdown in vitro and in vivo CD73. Upon nasal delivery of NE-siRNA CD73R, the treatment markedly reduced tumor volume by 60% in a rat preclinical glioblastoma model. The treatment was well tolerated, and did not induce kidney, liver, lung, olfactory, bone marrow, or behavior alterations. These results indicate that the nasal administration of NE as a CD73 siRNA delivery system offered an efficient means of gene knockdown and may represent a potential alternative for glioblastoma treatment.

Phase transitions in phospholipid monolayers: Statistical model at the pair approximation.

A Langmuir film, consisting of a phospholipid monolayer at the air-water interface, was modeled as a two-dimensional lattice gas corresponding to a ternary mixture of water molecules (w), ordered-chain lipids (o), and disordered-chain lipids (d). The statistical problem is formulated in terms of a spin-1 model, in which the disordered-chain lipid states possess a high degenerescence ω≫1, and was termed Doniach lattice gas (DLG). Motivated by some open questions in the analysis of the DLG model at the mean-field approximation (MFA) [Phys. Rev. E 90, 052705 (2014)PLEEE81539-375510.1103/PhysRevE.90.052705], we have reconsidered it at the pair-approximation level by solving the model on a Cayley tree of coordination z. The attractors of the corresponding discrete-map problem are associated with the thermodynamic solutions on the Bethe lattice (the central region of an asymptotically infinite Cayley tree). To check the thermodynamic stability of the possible phases, the grand-potential density was obtained by the method proposed by Gujrati [Phys. Rev. Lett. 74, 809 (1995)PRLTAO0031-900710.1103/PhysRevLett.74.809]. In general, the previous MFA results are confirmed at the pair-approximation level, but a novel staggered phase, overlooked in the MFA analysis, was found when the condition ε_{wd}>1/2(ε_{ww}+ε_{dd}) is satisfied, where ε_{xy} represents the nearest-neighbor intermolecular interactions between single-site states x and y. Model parameters obtained by fitting to experimental data for the two most commonly studied zwitterionic phospholipids, 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), yield phase diagrams consistent with the phase transitions observed on Langmuir films of the same lipids under isothermal compression, which present a liquid-condensed to a liquid-expanded first-order transition line ending at a critical point.

Does caffeine ingestion before a short-term sprint interval training promote body fat loss?

We investigated the effect of caffeine ingestion combined with a 2-wk sprint interval training (SIT) on training-induced reductions in body adiposity. Twenty physically-active men ingested either 5 mg/kg of cellulose as a placebo (PLA, n=10) or 5 mg/kg of caffeine (CAF, n=10) 60 min before each SIT session (13×30 s sprint/15 s of rest). Body mass and skinfold thickness were measured pre- and post-training. Energy expenditure was measured at rest, during exercise, and 45 min after exercise in the first SIT session. Body fat was similar between PLA and CAF groups at pre-training (P>0.05). However, there was a significant decrease in body fat after training in the CAF group (-5.9±4.2%, P<0.05) but not in PLA (1.5±8.0%, P>0.05). There was no difference in energy expenditure at rest and during exercise between PLA and CAF groups (P>0.05), but the post-exercise energy expenditure was 18.3±21.4% greater in the CAF than in the PLA group (P<0.05). In conclusion, caffeine ingestion before SIT sessions induced a body fat loss that may be associated with higher post-exercise energy expenditure.